Report of the committee on the genetic constitution of chromosome 17

Solomon, E.; Ledbetter, D.H.; Borrow, J.

doi:10.1159/000133177

Cited by 35 publications

(2 citation statements)

References 23 publications

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“…The region on 17q is telomeric to the ERBB2 and BRCAI genes and is amplified independently ofERBB2. This region appears fairly large and contains many candidate genes (e.g., HOX2, NGFR, PRKCA, HLRl, NMEl) (20). The region in 20q13 is defined by a fractional length (from pter) of -0.8.…”

Section: Methodsmentioning

confidence: 99%

Detection and mapping of amplified DNA sequences in breast cancer by comparative genomic hybridization.

Kallioniemi

Piper

et al. 1994

Proc. Natl. Acad. Sci. U.S.A.

649

433

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Comparative genomic hybridization was applied to 5 breast cancer cell lHes and 33 primary tumors to discover and map regions of the genome with increased DNAsequence copy-number. Two-thirds of primary tumors and almost all cell lines showed increased DNA-sequence copynumber affecting a total of 26 chromosomal subregions. Most of these loci were distinct from those of currently known amplified genes in breast cancer, with sequences originating from 17q22-q24 and 20q13 showing the highest frequency of amplification. The results indicate that these chromosomal regions may contain previously unknown genes whose increased expression contributes to breast cancer progression.Chromosomal regions with increased copy-number often spanned tens of Mb, suggesting involvement of more than one gene in each region.Increased expression of specific genes plays an important role in the pathogenesis of solid tumors (1-3). Gene amplification, characterized by distinct cytogenetic structures, such as homogeneously stained regions, double-minute chromosomes (1-7), is commonly found in tumor cells and is considered an important mechanism by which tumor cells gain increased levels of expression of critical genes. Increased copy-numbers also occur as a result of extensive chromosomal rearrangements, such as duplications, isochromosomes, extra marker chromosomes, and acentric chromosomal fragments that may affect the gene dosage of numerous genes simultaneously. In breast cancer, cytogenetic evidence of increased DNA-sequence copy-number is common (4-7). For example, homogeneously stained regions have been found in 60% of primary breast carcinomas (7). Although genetic analysis has found amplification of oncogenes, such as ERBB2 (17q12), MYC (8q24), PRADII CYCLIN D (11q13), FLG (8p12), BEK (10q24), and IGFR-1/FES (15q24-q25) (8-12), in most cases these do not explain the presence of large homogeneously stained regions (13). Thus, amplification of currently unknown genes may often occur in breast cancer.We have recently developed a method, comparative genomic hybridization (CGH), for surveying entire genomes for DNA-sequence copy-number variation (14, 15). In CGH, the relative intensities of tumor DNA (detected using green fluorescence) and normal reference DNA (detected with red fluorescence) after hybridization to normal metaphase chromosomes is used to reveal and map regions of increased DNA-sequence copy number (14-16). These loci are visualized as chromosomal region(s) with predominantly green fluorescence ( Fig. 1) and quantified by digital image analysis as an increased green-to-red fluorescence intensity ratio (Fig. 2). As no specific probes or previous knowledge of aberrations is required, CGH is especially suitable for identification and mapping of previously unknown DNA copy-number changes that may highlight locations of important genes. In the present study, we have used CGH to identify and map increases in DNA-sequence copy number in 15 breast cancer cell lines and 33 uncultured primary breast tumors. MATERIALS AND ME...

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Section: Methodsmentioning

confidence: 99%

Detection and mapping of amplified DNA sequences in breast cancer by comparative genomic hybridization.

Kallioniemi

Piper

et al. 1994

Proc. Natl. Acad. Sci. U.S.A.

649

433

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“…Hybrid clones were selected in hypoxanthine-aminopterin-thymidine (HAT) medium to retain human chromosome 17, or fragments derived from chromosome 17. which include the TK gene, located at 17q23.2-> q25.3 (Fain et al, 1991;Solomon and Ledbetter. 1991).…”

mentioning

confidence: 99%

Isolation and characterization of somatic cell hybrids with breakpoints spanning 17q22→q24

Flejter

Watkins²,

Abel³

et al. 1993

Cytogenet Genome Res

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Somatic cell hybrid mapping panels have previously been constructed to assist in the regional assignment of anonymous DNA probes and cloned genes to human chromosome 17. While a substantial number of hybrids are available that subdivide the short arm of this chromosome and the proximal portion of its long arm into specific regions, relatively few exist with breakpoints in the distal portion of the long arm. To increase the resolution of this region, four additional human × rodent somatic cell hybrids have been constructed that include breakpoints spanning the region 17q22→q24. Hybrid clones carrying the long-arm derivative of chromosome 17 were initially identified by fluorescence in situ hybridization. Hybrids were subsequently screened using the polymerase chain reaction with primer sets representing DNA markers previously mapped to chromosome 17. These hybrids expand the existing somatic cell hybrid panel for the distal portion of the long arm of chromosome 17.

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Prognostic significance of the loss of heterozygosity of nm23-h1 and p53 genes in human colorectal carcinomas

Campo¹,

Miquel²,

Jares³

et al. 1994

Cancer

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Background. Nm23 is a gene associated with low tumor metastatic potential and has been proposed to be a metastasis suppressor gene. Nm23 is localized on chromosome 17q21.3–22, whereas the p53 suppressor gene is on 17p13. Allelic deletions of chromosome 17 have been related to the progression of colorectal carcinomas. The purpose of this study was to analyze the allelic deletions of Nm23 and p53 in colorectal carcinomas and to assess their prognostic significance in the evolution of the patients. Methods. Allelic deletions of Nm23 and p53 genes were studied in 56 colorectal carcinomas using different restriction fragment length polymorphisms. DNA ploidy and proliferative activity of the tumors were studied by flow cytometry. Actuarial disease free and overall survival were analyzed by the Kaplan—Meier method, and the curves were compared with the log rank test. Results. Thirty‐eight patients were heterozygous for Nm23 gene (68%), and 9 of them (24%) exhibited a loss of heterozygosity in the tumor sample. One of the homozygous patients showed a loss of both Nm23 alleles. Allelic deletions of 17p13 were found in 63% of the 41 informative patients. All patients' tumors that had loss of heterozygosity of the Nm23‐H1 locus also had allelic losses on the short arm of chromosome 17 (17p13) and in other loci on 17q. No relationship was found between localization, invasion, lymph node metastasis, or proliferative index of the tumors and the allelic deletions of the Nm23‐H1 or 17p13 locus. Nm23‐H1 deletions were relatively more frequent in poorly differentiated adenocarcinomas (P = 0.03). A significant association between 17p13 deletions and DNA aneuploidy was found (P = 0.016). A similar tendency was observed with Nm23‐H1 deletions (P = 0.051). Loss of Nm23‐H1, but not of 17p13, was significantly associated with a shorter disease free (P = 0.025) and overall (P = 0.04) patient survival. Conclusions. Allelic deletions of Nm23‐H1 are significantly associated with a more aggressive behavior of colorectal carcinomas. The loss of this gene seems to be part of extensive deletions of chromosome 17, and it is also associated with DNA aneuploidy. More studies are needed to determine whether Nm23‐H1 or a gene linked to this locus is the specific target of the progression of these tumors. Cancer 1994; 73:2913–21.

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Report of the committee on the genetic constitution of chromosome 17

Cited by 35 publications

References 23 publications

Detection and mapping of amplified DNA sequences in breast cancer by comparative genomic hybridization.

Detection and mapping of amplified DNA sequences in breast cancer by comparative genomic hybridization.

Isolation and characterization of somatic cell hybrids with breakpoints spanning 17q22→q24

Prognostic significance of the loss of heterozygosity of nm23-h1 and p53 genes in human colorectal carcinomas

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